Effect of Carbohydrate Intake on Kidney Function and Structure in SHR/N-cp Rats: A New Model of NIDDM

Abstract

The SHR/N corpulent (cp) rat is a genetically obese rat that develops hyperglycemia, hyperinsulinemia, and proteinuria. This study was designed to evaluate the effects of high carbohydrate (CHO) intake on renal function and structure in this animal model and to determine whether the renal effects are related to the type of CHO ingested. Two groups of 5-wk-old obese male SHR/N-cp rats and lean male littermates were fed diets containing 54% CHO in the form of sucrose or starch. After 12 wk, renal function parameters, including creatinine clearance, urinary glucose excretion, and urinary protein excretion, were measured. Renal morphology was evaluated by semiquantitative light and electron microscopy. On either diet, obese rats had significantly higher urinary glucose and protein excretions than their lean littermates. Mean creatinine clearance (ml/min) in obese rats did not differ significantly from values observed in lean rats. When corrected for body weight, creatinine clearance (ml · min−1 · kg−1) tended to be lower in obese than in lean rats, but the difference was significant (P < .02) only for obese and lean sucrose-fed animals. Obese rats fed sucrose compared with their obese counterparts fed starch had higher body weight (+ 8%, P < .05), glucose excretion (+ 63%, P < .02), and protein excretion (+ 242%, P < .005). In obese rats, protein excretion correlated with glucose excretion (r = .71, P < .01). Glomerular lesions consisting of mesangial expansion and intercapillary nodules were found in obese but not in lean rats.Moreover, obese rats fed sucrose had a significantly greater number of involved glomeruli than obese rats fed starch. There was no evidence of glomerular basement membrane thickening in any of the animals studied. We conclude that the SHR/N-cp rat is sensitive to a high-CHO diet and develops glucosuria, proteinuria, renal insufficiency, and glomerular lesions resembling human diabetic nephropathy and that these characteristics are accentuated by high sucrose intake.